Testing sputum for three microRNA biomarkers may help identify cancerous lung nodules

Among patients who had an unidentifiable lung nodule detected by a chest CT scan, testing sputum for a panel of three microRNA (miRNA) biomarkers successfully distinguished early-stage lung cancers from nonmalignant nodules most of the time, according to a study published in Clinical Cancer Research (2015; doi:10.1158/1078-0432.CCR-14-1873).

“We are facing a tremendous rise in the number of lung nodules identified because of the increasing implementation of the low-dose CT lung cancer screening program,” said Feng Jiang, MD, PhD, an associate professor in the Department of Pathology at the University of Maryland School of Medicine in Baltimore. “However, this screening approach has been shown to have a high false-positive rate. Therefore, a major challenge is the lack of noninvasive and accurate approaches for preoperative diagnosis of malignant nodules.

“Our work may help address this important clinical challenge,” continued Jiang, who is also a researcher at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

“We developed and then validated a panel of three miRNA sputum biomarkers, miR-21, miR-31, and miR-210, that have the potential to help find lung cancer among indeterminate solitary pulmonary nodules that are initially found by CT scan. However, before these results can be translated into the clinic, we need to identify other biomarkers to add to the existing panel, to increase its sensitivity and specificity, and we need to evaluate the panel in a prospective clinical trial.”

Jiang and colleagues first tested the miRNA sputum biomarker panel in a group of 122 patients identified by chest CT scan to have a lung nodule. The test identified the 60 patients found to have lung cancer by invasive testing with 82.93% sensitivity and 87.85% specificity. This means that the test correctly predicted 82.93% of the time that a person with lung cancer had the disease, and it correctly predicted 87.85% of the time that a person without lung cancer did not have the disease.

In two independent groups of 136 and 155 patients with a lung nodule, the three-miRNA sputum biomarker panel had a sensitivity and specificity of 82.09% and 88.41%, and 80.52% and 86.06%, respectively.

“These values for sensitivity and specificity are not high enough for the three-biomarker panel to be used in the clinic,” said Jiang. “Because the specificity is only 87%, we cannot be certain enough that a patient does not have lung cancer. To be nearly certain whether a patient does or does not have lung cancer, the specificity of a test should be close to 100%.

“We are now applying new technologies to identify additional miRNA sputum biomarkers of lung cancer with the goal of expanding our biomarker panel to generate a test with high efficiency that can be practically used in clinical settings for lung cancer early detection,” added Jiang.

The study was supported by funds from the National Cancer Institute, the US Department of Veterans Affairs, and the LUNGevity Foundation. Jiang declares no conflicts of interest.